The implications of 18F-FDG PET for the diagnosis of endoprosthetic loosening and infection in hip and knee arthroplasty: Results from a prospective, blinded study

BACKGROUND: The most frequent complications of joint arthroplasty are septic or aseptic loosening of endoprostheses. Preoperative differentiation is essential, since very different treatment methods result from the diagnoses. The aim of the current study was to evaluate the clinical value of (18)F-Fluoro-deoxyglucose positron emission tomography ((18)F-FDG PET) as a diagnostic modality for inflammation and loosening in hip and knee joint prostheses. METHODS: (18)F-FDG-PET examinations and multiphase bone scan were performed on hip and knee endoprostheses in 27 patients prior to revision surgical procedures planned for prosthetic loosening. Intact prostheses were found at the opposite site in some patients so that additional 9 joints could be examined with the field of view of (18)F-FDG PET. Verification and valuation of the PET and scintigraphic image findings were conducted by comparing them with information combined from intraoperative findings, histopathology, and microbiological investigations. RESULTS: Evidence of loosening was correctly determined in 76.4% of cases using (18)F-FDG-PET, and in 75% of cases using bone scan. The detection of periprosthetic inflammation using (18)F-FDG-PET had a sensitivity of 100% for septic cases and of 45.5% in cases of increased abrasion and aseptic foreign-body reactions. However, reliable differentiation between abrasion-induced and bacterial-caused inflammation was not possible using (18)F-FDG-PET. CONCLUSION: (18)F-Fluoro-deoxyglucose positron emission tomography ((18)F-FDG-PET) allows reliable prediction of peri-prosthetic septical inflammatory tissue reactions. Because of the high sensitivity of this method, a negative PET result in the setting of a diagnostically unclear situation eliminates the need for revision surgery. In contrast, a positive PET result gives no clear differentiation regarding the cause of inflammation

Dispelling urban myths about default uncertainty factors in chemical risk assessment - Sufficient protection against mixture effects?

© 2013 Martin et al.; licensee BioMed Central LtdThis article has been made available through the Brunel Open Access Publishing Fund.Assessing the detrimental health effects of chemicals requires the extrapolation of experimental data in animals to human populations. This is achieved by applying a default uncertainty factor of 100 to doses not found to be associated with observable effects in laboratory animals. It is commonly assumed that the toxicokinetic and toxicodynamic sub-components of this default uncertainty factor represent worst-case scenarios and that the multiplication of those components yields conservative estimates of safe levels for humans. It is sometimes claimed that this conservatism also offers adequate protection from mixture effects. By analysing the evolution of uncertainty factors from a historical perspective, we expose that the default factor and its sub-components are intended to represent adequate rather than worst-case scenarios. The intention of using assessment factors for mixture effects was abandoned thirty years ago. It is also often ignored that the conservatism (or otherwise) of uncertainty factors can only be considered in relation to a defined level of protection. A protection equivalent to an effect magnitude of 0.001-0.0001% over background incidence is generally considered acceptable. However, it is impossible to say whether this level of protection is in fact realised with the tolerable doses that are derived by employing uncertainty factors. Accordingly, it is difficult to assess whether uncertainty factors overestimate or underestimate the sensitivity differences in human populations. It is also often not appreciated that the outcome of probabilistic approaches to the multiplication of sub-factors is dependent on the choice of probability distributions. Therefore, the idea that default uncertainty factors are overly conservative worst-case scenarios which can account both for the lack of statistical power in animal experiments and protect against potential mixture effects is ill-founded. We contend that precautionary regulation should provide an incentive to generate better data and recommend adopting a pragmatic, but scientifically better founded approach to mixture risk assessment. © 2013 Martin et al.; licensee BioMed Central Ltd.Oak Foundatio

Preclinical evaluation of two 68Ga-siderophores as potential radiopharmaceuticals for Aspergillus fumigatus infection imaging

PURPOSE: Invasive pulmonary aspergillosis is mainly caused by Aspergillus fumigatus, and is one of the major causes of morbidity and mortality in immunocompromised patients. The mortality associated with invasive pulmonary aspergillosis remains high, mainly due to the difficulties and limitations in diagnosis. We have shown that siderophores can be labelled with (68)Ga and can be used for PET imaging of A. fumigatus infection in rats. Here we report on the further evaluation of the most promising (68)Ga-siderophore candidates, triacetylfusarinine (TAFC) and ferrioxamine E (FOXE). METHODS: Siderophores were labelled with (68)Ga using acetate buffer. Log P, protein binding and stability values were determined. Uptake by A. fumigatus was studied in vitro in cultures with high and low iron loads. In vivo biodistribution was determined in normal mice and an infection model was established using neutropenic rats inoculated with A. fumigatus. Static and dynamic muPET imaging was performed and correlated with CT images, and lung infection was evaluated ex vivo. RESULTS: (68)Ga-siderophores were labelled with high radiochemical purity and specific activity. (68)Ga-TAFC and (68)Ga-FOXE showed high uptake by A. fumigatus in iron-deficient cultures. In normal mice, (68)Ga-TAFC and (68)Ga-FOXE showed rapid renal excretion with high metabolic stability. In the rat infection model focal lung uptake was detected by muPET with both compounds and increased with severity of the infection, correlating with abnormal CT images. CONCLUSION: (68)Ga-TAFC and (68)Ga-FOXE displayed excellent in vitro stability and high uptake by A. fumigatus. Both compounds showed excellent pharmacokinetics, highly selective accumulation in infected lung tissue and good correlation with severity of disease in a rat infection model, which makes them promising agents for A. fumigatus infection imaging

Guidelines for the labelling of leucocytes with 111In-oxine

We describe here a protocol for labelling autologous white blood cells with 111In-oxine based on previously published consensus papers and guidelines. This protocol includes quality control and safety procedures and is in accordance with current European Union regulations and International Atomic Energy Agency recommendations

Probabilistische assessment factoren voor de humane risicobeoordeling - Een practische gids

This report is a practical guide for the application of probabilistic distributions of default assessment factors in human health risk assessments. RIVM and TNO developed the use of probabilistic assessment factors as a first step towards further national and international harmonisation. Consensus was reached on the nature of distributions of several human assessment factors. The proposed distributions will be applied in risk assessments of new and existing substances and pesticides, produced at RIVM and TNO. A format for this analysis is presented in this report.Dit rapport is een practische gids voor de toepassing van probabilistische verdelingen van default assessment factoren in risicobeoordelingen voor de mens. RIVM en TNO ontwikkelden het gebruik van probabilistische assessment factoren als eerste stap naar nationale en internaitonale harmonisatie. Er was overeenstemming over de aard van de verdelingen van verschillende humane assessment factoren. De voorgestelde verdelingen zullen worden toegepast in RIVM- en TNO-risicobeoordelingen van nieuwe en bestaande stoffen en bestrijdingsmiddelen. Een voorbeeld van een dergelijke analyse is toegevoegd

Probabilistische assessment factoren voor de humane risicobeoordeling - Een practische gids

Dit rapport is een practische gids voor de toepassing van probabilistische verdelingen van default assessment factoren in risicobeoordelingen voor de mens. RIVM en TNO ontwikkelden het gebruik van probabilistische assessment factoren als eerste stap naar nationale en internaitonale harmonisatie. Er was overeenstemming over de aard van de verdelingen van verschillende humane assessment factoren. De voorgestelde verdelingen zullen worden toegepast in RIVM- en TNO-risicobeoordelingen van nieuwe en bestaande stoffen en bestrijdingsmiddelen. Een voorbeeld van een dergelijke analyse is toegevoegd.This report is a practical guide for the application of probabilistic distributions of default assessment factors in human health risk assessments. RIVM and TNO developed the use of probabilistic assessment factors as a first step towards further national and international harmonisation. Consensus was reached on the nature of distributions of several human assessment factors. The proposed distributions will be applied in risk assessments of new and existing substances and pesticides, produced at RIVM and TNO. A format for this analysis is presented in this report.RIV